Autoreactivity of T cells from nonobese diabetic mice: an I-Ag7-dependent reaction.
Mice bearing the I-Ag7 class II major histocompatibility complex molecules contain a high number of spontaneous autoreactive T cells, as estimated by limiting-dilution assays. We found this autoreactivity in various strains that bear the I-Ag7 molecule, such as the nonobese diabetic (NOD) mouse strain, which spontaneously develops autoimmune diabetes. However, NOD mice strains that do not express the I-Ag7 molecule, but instead express I-Ab, do not have a high incidence of autoreactive T cells. About 15% of the autoreactive T cells also recognize the I-Ag7 molecule expressed in the T2 line, which is defective in the processing of protein antigens. We interpret this to mean that some of the T cells may interact with class II molecules that are either devoid of peptides or contain a limited peptide content. We also find a high component of autoreactivity among antigen-specific T cell clones. These T cell clones proliferate specifically to protein antigens but also have a high level of reactivity to antigen-presenting cells not pulsed with antigen. Thus, the library of T cell receptors in NOD mice is skewed to autoreactivity, which we speculate is based on the weak peptide-binding properties of I-Ag7 molecules.
Kanagawa
O
O
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Martin
S M
SM
Vaupel
B A
BA
Carrasco-Marin
E
E
Unanue
E R
ER
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin